We propose to continue investigations of the genetic and toxic causes of mental retardation. In respect to this, the emphasis will be on mucolipidosis II (I-cell disease) and mucolipidosis III, the newly described entity of sialidase deficiency and on genetically-determined disorders of myelin, such as adrenoleukodystrophy and Refsum's disease. We will continue our evaluation of plasmapheresis as a therapeutic adjuvant in Refsum's disease and Fabry disease. Our studies of the genetics of certain forms of dyslexia are being continued. The toxicological studies will focus on the interactions between lead, zinc and other metals and on the development of an early biochemical marker of lead-induced brain dysfunction.